1. Field of the Invention
The present invention provides a blood sugar-modulating polypeptide and its use, especially to a polypeptide with the following amino acid sequence or a homologous amino acid sequence derived from the substitution, deletion, and/or addition of one or more amino acids therein:
RVRVWVTERGIVARPPTIG(SEQ ID NO. 11).
2. Descriptions of the Related Art
Diabetes is a chronic illness of metabolic abnormality. The main cause of diabetes is a lack of insulin, a defective function of insulin in the body, or the resistance to insulin caused by the combination of innate gene defects and the postnatal environment, leading to the low ability of using sugar, or even leading to the complete loss of the ability, thus further elevating blood sugar and abnormalizing the metabolism of proteins and lipids in the body. In addition, diabetes brings other chronic complications, including the pathological changes of the ocular fundus, nerve (including motor nerve, sensory nerve, and autonomic nerve), kidney, great vessels (including cerebrovascular obstruction, coronary artery disease, the occlusion of peripheral vessels), diabetes foot, etc.
According to the statistics from the World Health Organization (WHO), the number of diabetes patients around the world has increased dramatically, from about 30 million in 1985 to about 135 million in 1995, and to more than 177 million at present. The WHO further indicates that the number of worldwide diabetes patients will be more than 336 million in 2030. Moreover, the medical cost for diabetes and its complications in the U.S. increased from 44 billion USD in 1997 to 132 billion USD in 2000. With the increased prevalence of diabetes, it is important to develop a substance or medication that can modulate blood sugar efficiently.
Since 1922, insulin has been mainly used for treating diabetes. However, the lack of insulin is only part of the cause for the abnormality of pancreas function. Hence, using insulin individually to treat diabetes has limited efficiency.
Besides insulin, there are other pharmaceutical agents used to treat diabetes. These pharmaceutical agents, used for reducing blood sugar, can be classified into five groups according to their mechanisms. The first group consists of sulfonylureas, which promote the secretion of insulin from the pancreas and increase the number of insulin receptors of histiocytes. The second group consists of benzoic acid derivatives, capable of stimulating the secretion of insulin. The third group consists of biguanides, which inhibit the absorption of sugar in the stomach or intestine, inhibit the production of sugar in the liver, and promote the intake of sugar in tissues. The fourth group consists of α-glucosidase inhibitors, which prevent disaccharides from being degraded into monosaccharides so they can be absorbed by the intestines. The fifth group consists of insulin sensitizers, which alleviate the resistance of peripheral tissues and hepatocytes to insulin. Nevertheless, each group of the aforesaid pharmaceutical agents has different side effects. For example, sulfonylureas may cause rashes and a low level of blood sugar; benzoic acid derivatives may decrease the level of blood sugar; biguanides may cause lactic acidosis and stomach and intestine illnesses; α-glucosidase inhibitors may cause stomach and intestine illnesses; and insulin sensitizers may lead to the abnormality of liver function and injury to hepatocytes. Accordingly, it is important to develop medication with a blood sugar-modulating function and without side effects.
Unlike common compounds, polypeptides have better metabolizability and receptibility for organisms, and thus have fewer side effects. Therefore, many polypeptides have been studied in the world for decades and have been applied in clinical treatment. For instance, TW 1283684 discloses a Glucagon-Like Peptide-1 analogue, which reduces blood sugar, while U.S. Pat. No. 7,393,919 discloses medication for reducing blood sugar using Human prolslet Peptide (HIP), wherein the HIP is an active fragment of a pancreatitis-associated protein precursor.
Furthermore, polypeptides have been found to have blood sugar-reducing activity and can be obtained from plant extracts. For example, U.S. Pat. No. 6,127,338 discloses a polypeptide with blood sugar-reducing activity from bitter melon. The amino acid sequence of the polypeptide is KTNMKHMAGAAAAGAVVG (SEQ ID NO. 13), and the molecular weight of the polypeptide is less than 10 kDa.
Consequently, even though there are a lot of pharmaceutical agents for modulating blood sugar, a single or combined treating method or a pharmaceutical composition for treating diabetes with different morbific mechanisms is still needed.
The present invention researches the aforesaid requirement, and provides a novel polypeptide with a blood sugar-modulating function, especially a blood sugar-modulating function for animals in the normal state or in the diabetic state.